The Effects of Vasoactive Agents on Impedance Measures in the Pulmonary Circulation of Mice

Pulmonary hypertension is a potentially fatal disease, resulting from chronic obstructive or interstitial lung disease, recurrent pulmonary emboli, antecedent heart disease, hypoxia or other unknown causes [1]. Pulmonary hypertension causes vascular remodeling with smooth muscle cell (SMC) hyperplasia and hypertrophy and accumulation of collagen and elastin [2]. This remodeling increases pulmonary vascular resistance, which can lead to increases in steady right ventricular work [3]. The effects of remodeling on pulmonary vascular impedance, which determines pulsatile right ventricular work, remain incompletely described. We have previously quantified the effects of chronic hypoxia-induced pulmonary hypertension (HPH) on pulmonary vascular impedance [4] but did not investigate the role of SMC tone either before or after HPH. The aim of this study was to investigate the effects of normal and increased SMC tone on pulsatile pulmonary hemodynamics before and after HPH-induced pulmonary vascular remodeling. We hypothesized that SMC contraction would increase input resistance but decrease the speed of wave reflections. We also hypothesized that increased arteriolar muscularization after HPH would lead to greater increases in resistance and greater decreases in wave reflections with increased SMC tone.